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Thanks for the reply, and sorry for being slow to get back to you. I'm not trying to give you a hard time, just understand what you're really proposing.

For the record, I briefly looked into embryo screening when I was trying to have children but it seemed like we're not quite there yet. And IVF is such a pain in the ass that the only people who really go through with it really want a child.

I don't think it's necessary to use for every birth, just consistent usage for people who struggle with pregnancy in the first place & people with certain known problems (I'm deliberately vague here because I think there is a wide range of reasonable policies that should be subject to debate by both the public and experts to collectively find out what we find or find not adequate to select against) is likely to be sufficient to make effective dysgenics per generation almost zero or even turn it around.

I'm seeing only around 2% of people use IVF; why would you think they're the main potential drivers of (hypothetical) dysgenics? Most people around here seem to have 'welfare queens' in mind when discussing dysgenics. Note also that prenatal screening can have a pretty drastic effect, although I suppose many of the disorders you catch would be individuals who wouldn't go on to reproduce regardless so you may discount them.

From the initial data I've seen, simple general-health PGS is likely to even substantially improve the chances for a successful pregnancy beyond what the existing standard tests do, so it's win-win for absolutely everyone.

I can believe it.

Make sequencing (again, deliberately vague because while I think deep WGS should be the goal, WES, larger SNP arrays, etc. would be a big step up compared to current practice)

I've mostly focused on Mendelian disorders, but would you still be able to generate a PGS with whole exome? Or are you just looking for Mendelian diseases? Most of the well-validated genes are already tested for, whereas the disorders with a couple dozen known patients are more likely to just return VUS (variants of unknown significance) which aren't really actionable.

Over time, success and normalisation would increase the take-up and hence costs, but - and here you can call me out I guess - I think the scaling will more than make up for it.

I'm sure scale-up will factor in somehow, I just have no idea what order of magnitude to expect. The sequencing costs would probably scale. Analyzing the data and other bullshit probably wouldn't, unless we can get AI integrated into the healthcare system in some form or another. Hiring thousands of bioinformaticians, clinicians, nurses, lab techs, etc. would be a nightmare.

I'm not against what you're saying in broad strokes; I think something like this is coming sooner or later. I think it'll look a bit different than you outline, but maybe that's just splitting hairs. We'll almost certainly have the technology in place long before the public is anywhere close to accepting genetically engineered babies. It doesn't help that the godmother of CRISPR is profoundly decelerationist.

No problem, as you see I can be even slower, especially over the weekend when I'm barely touching my computer.

For the record, I briefly looked into embryo screening when I was trying to have children but it seemed like we're not quite there yet. And IVF is such a pain in the ass that the only people who really go through with it really want a child.

On my side, I also looked into embryo screening for our first child, and I briefly worked for an embryo screening company in the past. Similar to my proposal, I'd advise people to get themselves sequenced if they can afford it, and that they only should do embryo screening if there are specific reasons, such as that they already do IVF anyway or that they have higher risks for a serious disease based on their preliminary screening, score low on a general health PGS, etc. Btw, I'm also not opposed to germ cell selection since this came up somewhere else, but I'm not aware of this being an actual possibility at the moment.

I'm seeing only around 2% of people use IVF; why would you think they're the main potential drivers of (hypothetical) dysgenics? Most people around here seem to have 'welfare queens' in mind when discussing dysgenics. Note also that prenatal screening can have a pretty drastic effect, although I suppose many of the disorders you catch would be individuals who wouldn't go on to reproduce regardless so you may discount them.

As I wrote, I'd also advice people with a bad general health PGS/high risk for specific diseases etc. to get embryo screening, on a similar magnitude to the number of people who get IVF. So I don't think the IVF population is THE only main driver. But I do think the IVF population is very disproportionally an issue because they consistently have a much higher risks for almost every genetic/biological abnormality and this is often the reason for the pregnancy to fail in the first place. Sometimes because the parents are already unknowing carriers of something, sometimes the parents are even noticeably disabled themselves, and sometimes because the mother simply waited far too long (40+ the disability risk for children goes through the roof that mostly are down to genetics). On the other point, despite the cliche that someone like me who believes in HBD and advocates embryo screening necessarily thinks that everything is genetics, I'd actually still attribute ~50% of most things to environmental effects. "Welfare queens", by the usual definition, are actually capable of work, they merely refuse to. And they very disproportionally are part of a culture that tolerates or even encourages this behaviour. I consider dysgenics, which actually makes you less capable of working, a related but not entirely identical issue.

I've mostly focused on Mendelian disorders, but would you still be able to generate a PGS with whole exome? Or are you just looking for Mendelian diseases? Most of the well-validated genes are already tested for, whereas the disorders with a couple dozen known patients are more likely to just return VUS (variants of unknown significance) which aren't really actionable.

The most comprehensive currently available risk scores I'm aware of, such as genomic prediction's embryo health score or the UKBB PGS release, are just based on genotyped SNPs or WES at best. WGS (ideally including SVs) would be optimal of course, but isn't really sufficiently available. You don't need to only look at monogenic/mendelian disorders. It works fine in practice for most reasonably common polygenic attributes/diseases, because even if you have an attribute that is associated with, say, 10.000 variants, then not a single of those needs to be significant for the score as a whole to be significant. But it's true that very rare diseases are still a problem. But also by definition they're not actually the most pressing issue, so it's fine if we can't act on them for the time being.

Most people around here seem to have 'welfare queens' in mind when discussing dysgenics.

And that’s interesting because as far as I can tell, the high TFR for very low incomes is driven by illegals picking fruit and Hasidic Jews not wanting day jobs, Shaniqua in the ghetto having 5 children was a 90’s stereotype and not one with a huge amount of basis in present-day fertility rates.

Instead the bigger driver of dysgenics looks to be the divergence between the TFR’s of college and high school educated women(I think the above replacement TFR for women with less than a high school diploma is mostly confounders and that it’s a small enough population for that to be the case).